四川大学邓东团队取得一项新突破。他们开发出小鼠细胞质晶格结构。2026年3月31日出版的《自然》杂志发表了这项成果。

该研究团队报道了3.74Å分辨率的天然小鼠CPL重复单元（~4MDa）的冷冻-EM结构。这个重复单元展示了一个由框架、扩展连接器和CPL核心组成的三方体系结构。外部框架是由PADI6十轴体和皮质下母体复合物（SCMC）构建的。由NLRP4F形成的两个连接体将框架聚合成延伸的丝。在CPL核心中，表观遗传调控因子UHRF1被PADI6、UBE2D和NLRP14捕获，形成致密的自抑制构象，阻止核进入和泛素连接酶活性。

此外，CPL核心储存GTP结合的α/β-微管蛋白异源二聚体和无活性的SCF E3-泛素连接酶组分（FBXW-SKP1复合物）处于平衡但受抑制的状态。这些特征使CPL成为一个动态的调控池，在卵母细胞向胚胎转变的过程中，它能够实现快速的微管组装和严格控制的泛素化。总之，这种半原位结构阐明了CPL的组装和存储模块组织，并确立了CPL作为母体在卵母细胞和早期胚胎发育中调节的专门的蛋白质平衡细胞器。

据了解，受精卵几乎完全依靠母体卵母细胞的储存来确保发育的成功开始。哺乳动物卵母细胞中的细胞质晶格（CPL）储存着母体表达的蛋白，在胚胎发生中起着重要作用。损伤多个CPL成员导致早期胚胎停止（EEA），导致哺乳动物不孕。然而，CPL的组装和储存机制在很大程度上仍然是未知的。

附：英文原文

Title: Structure of the mouse cytoplasmic lattice

Author: Chi, Pengliang, Wang, Xiang, Li, Jialu, Huang, Jingrui, Ju, Sicheng, Liu, Sibei, Yan, Li, Lu, Yuechao, Zhang, Zihan, Han, Zhuo, Li, Jinhong, Qi, Qianqian, Liu, Qingting, Zeng, Yiren, Guo, Li, Zhang, Xiaofeng, Gui, Long, Deng, Dong

Issue&Volume: 2026-03-31

Abstract: The fertilized egg relies almost entirely on maternal stores in the oocyte to ensure the successful initiation of development1. The cytoplasmic lattices (CPLs) in mammalian oocytes store maternal-expressed proteins and play an essential role in embryogenesis2,3. Impairing multiple CPL members leads to early embryonic arrest (EEA), resulting in infertility in mammals. However, the mechanism underlying the assembly and storage of CPLs remains largely unknown. Here, we report the cryo-EM structure of a native mouse CPL repeating unit (~ 4 MDa) at 3.74 resolution. This repeating unit exhibits a tripartite architecture comprising a framework, extended linkers, and a CPL core. The external framework is built from PADI6 decamers and the subcortical maternal complexes (SCMC). Two linkers formed by NLRP4F polymerize the frameworks into an extended filament. In CPL core, the epigenetic regulator UHRF1 is trapped by PADI6, UBE2D, and NLRP14 in a compact, autoinhibited conformation that prevents nuclear entry and ubiquitin ligase activity. Moreover, the CPL core stores GTP-bound α/β-tubulin heterodimers and inactive SCF E3-ubiquitin ligase components (FBXW-SKP1 complex) in a poised but restrained state. These features establish CPLs as a dynamic regulatory pool that enables rapid microtubule assembly and tightly controlled ubiquitination during the oocyte-to-embryo transition. Together, this semi-in-situ structure illuminates CPL assembly and storage-module organization, and establishes CPLs as specialized proteostasis organelles for maternal regulation in oocytes and early embryonic development.

DOI: 10.1038/s41586-026-10442-6

Source: https://www.nature.com/articles/s41586-026-10442-6